Assisted fertilization, such as in vitro fertilization (IVF), has been used in human subjects with infertility problems successfully for three decades. Despite extensive research, it is still a difficult and expensive procedure. Indeed, less than 5% of oocytes collected and only 20-25% of embryos transferred lead to a birth. Optimization of embryo competence as well as corresponding uterine receptivity is an absolute requirement to improve success in assisted reproductive technology (ART). The success of implantation involves a synchronized crosstalk between a receptive endometrium and a functional blastocyst. This phenomenon can only take place during the window of implantation, a self-limited period of endometrial receptivity spanning between days 19 and 23 of the menstrual cycle (women). In normal menstrual cycles this is achieved through the local effects of ovarian estrogens and progesterone, which induce a series of cellular and molecular events in the endometrium leading to appropriate endometrial receptivity.
Methods for determining endometrial receptivity have been disclosed in the art: for example, U.S. Pat. No. 7,175,990 disclosed a method based on the determination of L-selectin level produced by uterine epithelial cells, wherein an increase in the L-selectin level compared to a control level indicates an increased probability of success of implantation. Another method for determining endometrial receptivity disclosed in EP2348318 is based on the determination of prostaglandin E2 or F2 alpha level in endometrial fluid. Other emerging approach like the Endometrial Receptive array (ERA system) explored 238 genes specifically expressed during the implantation window (PCT/ES2009/000386). These methods are only useful for determining endometrial receptivity to embryo implantation.
However, in case of determination of inappropriate receptivity of the endometrium, these methods are unhelpful for restoring art endometrial receptivity.
The inventors have made the observation that the inappropriate receptivity of an endometrium can be explained by two different states: an under-activated state or an over-activated state. Determining an endometrial state thus allow explaining its non-receptivity, thereby leading to adapted and personalized treatment for restoring a receptivity state.
Consequently, it is of interest to provide a method allowing the determination of an endometrial state of a female subject, this information being useful to optimize her treatment for restoring an endometrial receptivity.